Twin-column affinity capture: current developments in continuous protein
A affinity chromatography


*Corresponding author
1. Department for Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland
2. ChromaCon AG, Zurich, Switzerland


In protein A affinity chromatography, the cost of the solid phase constitutes a major part of the overall production cost. Therefore, maximizing resin capacity utilization is an important way of optimizing the economic aspects of monoclonal antibody production. This work presents and explores the twin-column CaptureSMB process, a novel cyclic counter-current chromatographic capture process. In order to assess potential performance gains, the CaptureSMB process was compared to traditional batch capture run at different loading flow rates. The CaptureSMB process showed superior performance in terms of capacity utilization, productivity, product concentration and buffer consumption, while retaining the same product quality attributes and yield. This resulted in significant potential economic benefits.


Monoclonal antibodies (mAbs) and products derived from mAbs (such as mAb fragments, fusion proteins, antibody-drug-conjugates, etc.) have become the most important growing market for biopharmaceuticals in the last decade (1).

In such a fast developing and competitive environment, it is paramount to strive for optimal production conditions. Since protein A affinity chromatography is still the main capture step in downstream processing of mAbs, optimizing this step in particular is of utmost importance (2). Even though the price of this affinity resin is almost one order of magnitude higher than the price of non-affinity materials, it is still the only established option to reach the required purity levels.

Typically, protein A capture processes are run in batch mode, where a single column is loaded up to its dynamic binding capacity (DBC) at a certain level of breakthrough. Typically 90% of the load volume required to reach 1% DBC is chosen to avoid any product losses due to packing variability and resin deterioration by ligand leeching and irreversible adsorption of impurities (3). This volume depends on the shape of the brea ...